ArticleSignal transduction and targeted therapy2025
Olverembatinib, a multikinase inhibitor that modulates lipid metabolism, in advanced succinate dehydrogenase-deficient gastrointestinal stromal tumors: a phase 1b study and translational research.
Article in Signal transduction and targeted therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03594422 (A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of Oral HQP1351 in Patients With GIST or Other Solid Tumors.), which is not on this map. Cited by 5 papers.
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The trial behind it
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A Phase I Study to Assess the Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of Oral HQP1351 in Patients With GIST or Other Solid Tumors.
Who cites it
5 citing papers in PubMed.
- Article
- Targeting the Unmet Need in Gastrointestinal Stromal Tumors: A Contemporary Review of Investigational Clinical Trials and Therapeutic Landscape.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Targeted Therapy for Advanced Gastrointestinal Stromal Tumors: Evolution and Future Directions.Drug design, development and therapy · 2026Review
- Review
- RPL17 regulates the progression of breast cancer accompanied by MAPK signaling activation.Medical oncology (Northwood, London, England) · 2025Article
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19 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumors (GISTs) are generally resistant to targeted therapy with tyrosine kinase inhibitors (TKIs), such as imatinib, and there are no standard therapeutic options for advanced SDH-deficient GISTs. The precise oncogenic mechanisms of SDH mutations in GIST have not been elucidated. Olverembatinib, a novel multikinase inhibitor, has shown promising activity in treating imatinib-resistant GIST. We conducted a phase 1 study (NCT03594422) to evaluate the safety and antitumor activity of olverembatinib in 66 patients with unresectable/metastatic GIST/other solid tumors, including 26 with TKI-failed SDH-deficient GISTs. To our knowledge, this is the largest prospective clinical trial for this rare GIST subtype. The median follow-up was 14.5 (0.9-57.5) months. Olverembatinib was well tolerated; treatment-emergent adverse events (≥20%) included increases in hepatic transaminases, increases in leukocytes and neutrophils, anemia, and pyrexia. For SDH-deficient GISTs, confirmed partial responses were observed in 6 of the 26 evaluable patients (objective response rate, 23.1%; 95% CI, 9-43.7); an additional 16 (61.5%) did not progress during the first 6 months of treatment. This resulted in a clinical benefit rate of 84.6% (95% CI, 65.1-95.6), and the median progression-free survival was 25.7 months (95% CI, 12.9-NR). As a putative mechanism of action, translational research revealed significant lipid enrichment with the overexpression of lipid uptake-related genes and proteins, including CD36, fatty acid binding proteins, fatty acid transport proteins, and lipid metabolites, in SDH-deficient GIST patients, and olverembatinib suppressed lipid uptake and CD36 expression in GIST cells. Olverembatinib also exerts antitumor effects by inhibiting tumorigenic signaling pathways associated with hypoxia, angiogenesis, proliferation, and survival.
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